Abstract:
:Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, complications of pregnancy, cognitive impairment, and osteoporosis. That elevated homocysteine leads to vascular dysfunction may be the linking factor between these apparently unrelated pathologies. Although a growing body of evidence suggests that homocysteine plays a causal role in atherogenesis, specific mechanisms to explain the underlying pathogenesis have remained elusive. This review focuses on chemistry unique to the homocysteine molecule to explain its inherent cytotoxicity. Thus, the high pKa of the sulfhydryl group (pKa, 10.0) of homocysteine underlies its ability to form stable disulfide bonds with protein cysteine residues, and in the process, alters or impairs the function of the protein. Studies in this laboratory have identified albumin, fibronectin, transthyretin, and metallothionein as targets for homocysteinylation. In the case of albumin, the mechanism of targeting has been elucidated. Homocysteinylation of the cysteine residues of fibronectin impairs its ability to bind to fibrin. Homocysteinylation of the cysteine residues of metallothionein disrupts zinc binding by the protein and abrogates inherent superoxide dismutase activity. Thus, S-homocysteinylation of protein cysteine residues may explain mechanistically the cytotoxicity of elevated L-homocysteine.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Glushchenko AV,Jacobsen DWdoi
10.1089/ars.2007.1809subject
Has Abstractpub_date
2007-11-01 00:00:00pages
1883-98issue
11eissn
1523-0864issn
1557-7716journal_volume
9pub_type
杂志文章,评审abstract:SIGNIFICANCE:Glutaredoxins are ubiquitous small thiol proteins of the thioredoxin-fold superfamily. Two major groups are distinguished based on their active sites: the dithiol (2-C-Grxs) and the monothiol (1-C-Grxs) glutaredoxins with a CXXC and a CXXS active site motif, respectively. Glutaredoxins are involved in cell...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4932
更新日期:2013-09-01 00:00:00
abstract:SIGNIFICANCE:Mitochondrial function is central to a wide range of biological processes in health and disease and there is considerable interest in developing small molecules that are taken up by mitochondria and act as either probes of mitochondrial function or therapeutics in vivo. RECENT ADVANCES:Various strategies ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.3969
更新日期:2011-12-15 00:00:00
abstract::This work rests on our previous report (J Cereb Blood Flow Metab 30: 1275-1287, 2010) recognizing that glutamate (Glu) oxaloacetate transaminase (GOT) is induced when brain tissue hypoxia is corrected during acute ischemic stroke (AIS). GOT can metabolize Glu into tricarboxylic acid cycle intermediates and may therefo...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.3930
更新日期:2011-05-15 00:00:00
abstract:SIGNIFICANCE:Heart disease is the primary cause of death in the industrialized world. Cardiac failure is dictated by an uncompensated reduction in the number of viable and fully functional cardiomyocytes. While current pharmacological therapies alleviate the symptoms associated with cardiac deterioration, heart transpl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.5875
更新日期:2014-11-10 00:00:00
abstract:SIGNIFICANCE:The accepted effects of aging in mammalian skeletal muscle are progressive atrophy and weakening, or sarcopenia. Canonical hallmarks of aging in skeletal muscle include a reduction in muscle fiber cross-sectional area, a loss in muscle fibers through apoptosis and denervation, and infiltration of connectiv...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.3974
更新日期:2011-11-01 00:00:00
abstract::Despite the significance of redox post-translational modifications (PTMs) in regulating diverse signal transduction pathways, the enzymatic systems that catalyze reversible and specific oxidative or reductive modifications have yet to be firmly established. Thioredoxin 1 (Trx1) is a conserved antioxidant protein that ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3831
更新日期:2011-11-01 00:00:00
abstract::Hydrogen sulfide (H(2)S) is a gasotransmitter with multifaceted physiological functions, including the regulation of glucose metabolism. Methylglyoxal (MG) is an intermediate of glucose metabolism and plays an important role in the pathogenesis of insulin resistance syndromes. In the present study, we investigated the...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2918
更新日期:2010-05-01 00:00:00
abstract::Transforming growth factor-betas (TGF-beta) regulate a wide variety of cellular functions in normal development and are involved in both tissue homeostasis and disease pathogenesis. The regulation of the TGF-beta family of growth factors is unique because they are targeted to the extracellular matrix in a biologically...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1914
更新日期:2008-02-01 00:00:00
abstract::Carica papaya Linn is widely known as a medicinal fruit. We sought to study a standardized fermented papaya preparation (FPP) for its effects on wound healing in adult obese diabetic (db/db) mice. FPP blunted the gain in blood glucose and improved the lipid profile after 8 weeks of oral supplementation. However, FPP d...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.3039
更新日期:2010-09-01 00:00:00
abstract:SIGNIFICANCE:The heme-enzyme myeloperoxidase (MPO) is one of the major neutrophil bactericidal proteins and is stored in large amounts inside azurophilic granules of neutrophils. Upon cell activation, MPO is released and extracellular MPO has been detected in a wide range of acute and chronic inflammatory conditions. R...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4783
更新日期:2013-02-20 00:00:00
abstract:SIGNIFICANCE:The circadian clock, an internal timekeeping system, is implicated in the regulation of metabolism and physiology, and circadian dysfunctions are associated with pathological changes in model organisms and increased risk of some diseases in humans. RECENT ADVANCES:Data obtained in different organisms, inc...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5671
更新日期:2014-06-20 00:00:00
abstract::Oxidative stress due to increased epidermal levels of H(2)O(2) with consequent inhibition of catalase activity is generally accepted as a leading cytotoxic mechanism of melanocyte loss in vitiligo. Keratinocyte-derived cytokines are considered key factors in the maintenance of melanocyte structure and functions. We hy...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2976
更新日期:2010-09-01 00:00:00
abstract::Thioredoxin (TRX) family proteins are involved in various biologic processes by regulating the response to oxidative stress. Nucleoredoxin (NRX), a relatively uncharacterized member of the TRX family protein, has recently been reported to regulate the Wnt/beta-catenin pathway, which itself regulates cell fate and earl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1550
更新日期:2007-08-01 00:00:00
abstract:SIGNIFICANCE:Mitochondria are double membrane-bound organelles with tubular network structures that are essential for oxidative ATP production and play pivotal roles in regulating calcium homeostasis and apoptosis. Furthermore, mitochondria produce large amounts of reactive oxygen species that are fatal to cellular fun...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4830
更新日期:2013-08-01 00:00:00
abstract:: Aims: Peroxisome is a critical organelle for fatty acid oxidation (FAO) and metabolism of reactive oxygen species (ROS). Increased oxidative stress in adipose tissue contributes to the development of insulin resistance and metabolic syndrome in obesity. This study aimed to...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2018.7614
更新日期:2019-12-20 00:00:00
abstract:AIMS:Pulmonary infections with Pseudomonas aeruginosa are a serious clinical problem and are often lethal. Because many strains of P. aeruginosa are resistant to antibiotics, therapeutic options are limited. Neutrophils play an important role in the host's early acute defense against pulmonary P. aeruginosa. Therefore,...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2014.5979
更新日期:2015-05-01 00:00:00
abstract:SIGNIFICANCE:Protein degradation has been identified as being deregulated in numerous human diseases. Hence, proteins involved in proteasomal as well as lysosomal degradation are regarded as interesting potential drug targets and are thoroughly investigated in clinical studies. RECENT ADVANCES:Technical advances in th...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.4393
更新日期:2012-09-01 00:00:00
abstract:AIMS:Chronic metabolic impairment and oxidative stress are associated with the pathogenesis of axonal dysfunction in a growing number of neurodegenerative conditions. To investigate the intertwining of both noxious factors, we have chosen the mouse model of adrenoleukodystrophy (X-ALD), which exhibits axonal degenerati...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3877
更新日期:2011-10-15 00:00:00
abstract::Although much is known about how TNF-alpha induces apoptosis in the presence of inhibitors of protein synthesis, little is known about how it induces apoptosis without these inhibitors. In this report we investigated temporal sequence of events induced by TNF-alpha in the absence of protein synthesis. Regardless of wh...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.3036
更新日期:2010-09-15 00:00:00
abstract:AIMS:Adenosine triphosphate (ATP) synthase uses chemiosmotic energy across the inner mitochondrial membrane to convert adenosine diphosphate and orthophosphate into ATP, whereas genetic deletion of Sirt3 decreases mitochondrial ATP levels. Here, we investigate the mechanistic connection between SIRT3 and energy homeost...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5420
更新日期:2014-08-01 00:00:00
abstract::Lisinopril is an inhibitor of the renin-angiotensin system. Does lisinopril minimize oxidative damage in spontaneously hypertensive rats (SHR) in comparison with the normotensive genetic controls Wistar Kyoto (WKY)? The authors note that lisinopril contained lipid peroxidation, elevated tissue glutathione levels, and ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2006.1477
更新日期:2007-03-01 00:00:00
abstract::The signaling for activation of protein tyrosine kinases (PTKs) is usually started by binding of ligands to cell-surface receptors. However, recent evidence suggests the presence of ligand binding-independent signaling pathways that are mediated by oxidative stress. Oxidation and reduction of protein cysteine sulfhydr...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/15230860260196326
更新日期:2002-06-01 00:00:00
abstract:SIGNIFICANCE:The thioredoxin (Trx) superfamily proteins, including protein disulfide isomerases (PDI) and Dsb protein family, are major players in oxidative protein folding, which involves native disulfide bond formation. These proteins contain Trx folds with CXXC active sites and fulfill their physiological functions ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.5849
更新日期:2014-07-20 00:00:00
abstract::Glutathione peroxidases and thioredoxin reductases are the main selenoproteins expressed by endothelial cells. These enzymes reduce hydroperoxides, their role in endothelial cell physiology, however, by far exceeds prevention of oxidative damage. Reactive oxygen and nitrogen species, especially superoxide, hydroperoxi...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308603764816569
更新日期:2003-04-01 00:00:00
abstract::The Arc two-component system is a complex signal transduction system that plays a key role in regulating energy metabolism at the level of transcription in bacteria. This system comprises the ArcB protein, a tripartite membrane-associated sensor kinase, and the ArcA protein, a typical response regulator. Under anoxic ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.781
更新日期:2006-05-01 00:00:00
abstract:SIGNIFICANCE:The 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors or statins are important therapeutic agents for lowering serum cholesterol levels. However, recent studies suggest that statins may exert atheroprotective effects beyond cholesterol lowering. These so-called "pleiotropic effects" include effects ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5524
更新日期:2014-03-10 00:00:00
abstract:AIMS:Aberrant Cdk5 (cyclin-dependent kinase 5) and oxidative stress are crucial components of diverse neurodegenerative disorders, including Alzheimer's disease (AD). We previously reported that a change in peroxiredoxin (Prx) expression is associated with protection from neuronal death. The aim of the current study wa...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6810
更新日期:2017-10-10 00:00:00
abstract:AIMS:Macrophages are of key importance for tissue repair after myocardial infarction (MI). Hydrogen sulfide (H2S) has been shown to exert cardioprotective effects in MI. However, the mechanisms by which H2S modulates cardiac remodeling and repair post-MI remain to be clarified. RESULTS:In our current study, we showed ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6577
更新日期:2016-08-10 00:00:00
abstract:SIGNIFICANCE:Cardiovascular diseases are the main cause of death worldwide and pose an immense economical burden. In most cases, the underlying problem is vascular occlusion by atherosclerotic plaques. Importantly, different cell types of the vascular wall and the immune system play crucial roles in atherosclerosis at ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2016.6946
更新日期:2017-05-01 00:00:00
abstract::Fluid shear stress plays a critical role in the regulation of vascular biology and its pathology, such as atherosclerosis, via modulation of redox balance. Both pro-atherogenic (either oscillatory or turbulent, nonunidirectional) shear stress and anti-atherogenic (either steady or pulsatile, unidirectional laminar) sh...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3433
更新日期:2011-09-01 00:00:00